The endogenous cannabinoid (endocannabinoid) system (ECS) plays an important role in intestinal physiology. Modulation of the ECS affects gastrointestinal motility and secretion and can influence epithelial integrity and immune function. Altered expression of the ECS may also modulate the pathophysiology of gastrointestinal disease, particularly in regards to the effects of endocannabinoids on gastrointestinal inflammation and linkages with functional clinical disorders characterized by altered motility. Implicit in the recognition of the pleitropic roles of the endocannabinoids is knowledge of their potential metabolic fate via multiple enzymatic pathways including fatty acid amido-hydrolase, cyclo-oxygenase (COX-2) and lipoxygenases. Such pathways may generate a multitude of biological intermediates or mediators with discreet cellular actions. This is in addition to the conferring of altered function via activation at conventional cannabinoid CB1 and CB2 receptor subtypes and possibly additional subtypes or orphan receptors. Further preclinical studies may yet reveal a therapeutic potential of exploiting the endocannabinoid system in the treatment of gastrointestinal disease states, particularly chronic inflammation.